This project is aimed at learning about the pathogenesis of immune-mediated eye diseases. The main effort has been focused on investigating an animal disease, experimental autoimmune uveitis (EAU), which is considered a model for certain eye diseases in man. EAU is induced by immunizing animals with a retinal protein, S-antigen, and may be adoptively transferred to naive animals by lymphocytes from immunized donors. Findings of note in the present studies include: 1. A correlation was found between the susceptibility to EAU and number of choroidal mast cells in rats of various inbred strains. This finding (a) supports the notion that mast cells play an important accwssory role in the induction of EAU, and (b) indicates that genetically regulated susceptibility to an autoimmune disease may be mediated in part by the number of mast cells at the target organ site. 2. Lymphocytes of the "helper/inducer" subset were identified to be the ones responsible for the adoptive transfer of EAU: lymphocytes of the "suppressor/cytotoxic" subset had no such activity. This finding defines the immunopathogenic mechanism of EAU to be of the "delayed type hypersensitivity" rather than the "cytotoxic" type. 3. EAU development may be modulated by drugs. Adoptive transfer of EAU was enhanced when preceded by a single injection of cyclophosphamide. On the other hand, actively induced EAU was inhibited or delayed by various immunosuppressive drugs when given during the disease induction. Of the drugs tested, cyclosporine was found to be superior by its low toxicity and high efficacy. In addition, the immunosuppressive effect of cylcosporine was found to be augmented by the development of specific immunotolerance to S-antigen in rats treated with this drug. The data slo show that EAU provides an experimental system for assessing different compounds for their effect on immune mediated eye disease.